The goal of this career development plan is to launch an independent research program in molecular epidemiology with specific emphasis on the evaluation of gene-environment interactions. To this end, it includes both didactic coursework and hands-on training in the areas of molecular biology/ genetics and molecular epidemiology. Melanoma is a unique model for studying gene-environment interactions as there is mounting evidence that low-penetrance genetic polymorphisms may moderate the melanoma risk of solar UV exposure. Genes of the base excision repair (BER) pathway repair DNA damage secondary to UVA exposure. The candidate will use the international Genes, Environment and Melanoma (GEM) 3366-subject case-control study as a platform to test the hypothesis that UV radiation and BER variants interactively affect melanoma risk. Lifetime sun exposure history and DNA specimens are available for each subject. The candidate's research will (a) determine the prevalence of BER variants in GEM melanoma cases and controls;(b) evaluate the interactive influence of candidate BER variants and chronic sun exposure on melanoma risk;and (c) investigate whether melanoma risk is influenced by gene-gene interactions between BER variants and variants in other genes currently being examined in the GEM study (MC1R and nucleotide excision repair genes) adjusting for sun exposure. This research proposal will provide the candidate with an appreciation for and understanding of the laboratory and epidemiologic analyses techniques needed to conduct molecular epidemiologic research on environmentally related diseases. Through intensive interactions with the GEM consortium and other multidisciplinary investigators, formal coursework in molecular biology and epidemiology, and research, this career development award will establish the candidate's multidisciplinary research skills at the interface of genetics, epidemiology and environmental health, and position her to establish novel theories regarding the mechanisms underlying complex genetic-environmental interactions in melanoma.